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Yves Panis

Publications and source records attributed to Yves Panis.

36 records · Page 2Linked to original sources
PubMed2004

Adjuvant interleukin-12 gene therapy for the management of colorectal liver metastases.

In humans, no efficient treatment exists not only against multifocal liver metastases (LM) but also against recurrent microscopic liver metastases within the liver remnant following curative liver resection. Furthermore, in nonmultifocal LM, partial liver resection could be performed, but in more than 50% of the patients, tumor recurrence within liver remnant is observed, partly due to the growth of dormant cancer cells in the setting of postoperative host immune dysfunction. We investigated the therapeutic potential of interleukin-12 (IL-12) immuno-gene therapies in these experimental models under total vascular exclusion (TVE) of the liver. In rats with multiple LM of DHDK12 colon cancer cells, we observed a significant reduction in tumor volume after retroviral-mediated gene transfer of either herpes simplex virus thymidine kinase (HSV1-TK) and ganciclovir (GCV) administration, or IL-12. Combined treatment with HSV1-TK/GCV and IL-12 resulted in improved tumor volume reduction and even survival. In rats with recurrent microscopic DHDK12 LM established after partial liver resection, we observed significantly decreased recurrent tumor volumes and increased survival after retroviral-mediated IL-12 gene transfer. In both settings, immunohistological analysis revealed that IL-12 immuno-gene therapy was accompanied by an infiltration of CD8+ T lymphocytes within the tumors. Altogether, our results suggest that IL-12 adjuvant gene therapy could improve the management of patients with either resectable or unresectable LM.

Animals↗
PubMed2004

Could immunosuppressive drugs reduce recurrence rate after second resection for Crohn disease?

BACKGROUND: The aim of this study was to assess the possible benefit of postoperative immunosuppressive drugs administration (ie, azathioprine, 6-mercaptopurine, or methotrexate) on long-term surgical recurrence rate after second anastomotic ileocolonic resection. METHODS: From 1984 to 2000, 26 patients with CD underwent second resection for ileocolonic anastomotic recurrence. There were 14 women and 12 men (mean age +/- SD: 34 +/- 9 years). Two groups of patients were compared according to the postoperative treatment: immunosuppressive (IS) drugs group was composed of 14 patients, and control group was composed of 12 patients receiving either salicylates (n = 5) or no treatment (n = 7). RESULTS: Clinical recurrence rate at 3 years was significantly lower in the IS group than in the control group (3/12, 25% vs 6/10, 60%; P < 0.05). Although not significant, after a mean follow-up of 80 +/- 46 months (extr. 17-178 months) after the second resection, clinical recurrence rate at follow-up was also lower in IS group (6/14, 43%) than in control group (9/12, 75%). The mean delay of recurrence was similar in both groups (27 +/- 13 months vs 28 +/- 21; NS). A third intestinal resection was performed less frequently in the IS group than in control group (2/14, 17% vs 7/12, 58%; P < 0.02). CONCLUSIONS: In patients treated with IS drugs, the rate of postoperative recurrence after second ileocolonic CD resection is lower than in untreated patients. Our results suggest that IS drugs should be evaluated prospectively for prevention of second postoperative CD recurrence.

Adult↗
PubMed2003

Subtotal colectomy for severe acute colitis: a 20-year experience of a tertiary care center with an aggressive and early surgical policy.

BACKGROUND: Management of severe acute colitis (SAC) complicating inflammatory bowel disease remains a challenge despite significant advances in medical therapy. The aim of this study was to report a 20-year experience with subtotal colectomy (STC) performed for SAC. STUDY DESIGN: A total of 164 consecutive patients with a mean age of 37 +/- 15 years (range 16 to 86 years) underwent STC for SAC defined according to the criteria of Truelove and Witts. The decision for surgical treatment was based on clinical, biologic, radiologic, and endoscopic severity criteria both at entry and during hospitalization after failure to improve under medical treatment. A Brooke ileostomy was made to the right iliac fossa and a sigmoidostomy was made to the midline incision. All complications before discharge were recorded as in-hospital morbidity or mortality. RESULTS: Colonoscopy was performed in 153 patients and endoscopic diagnosis of SAC was confirmed by pathologic examination in 84% of the cases. STC was performed on an emergency basis in 40 patients with complications and only after failure of medical treatment in the remaining 124 patients. The mortality rate was 0.6%. The overall morbidity rate was 33%; 24 patients required reoperation, including 8% undergoing reoperation during followup for small bowel obstruction. Definitive pathologic diagnosis changed in one half of the patients; the final diagnosis was Crohn's disease in 110 cases, ulcerative colitis in 35, and indeterminate colitis in 19. CONCLUSIONS: Our results demonstrated the safety of STC performed in a tertiary care center for patients with SAC who presented with complications or failed to respond to intensive medical therapy.

Acute Disease↗
PubMed2003

Methodological index for non-randomized studies (minors): development and validation of a new instrument.

BACKGROUND: Because of specific methodological difficulties in conducting randomized trials, surgical research remains dependent predominantly on observational or non-randomized studies. Few validated instruments are available to determine the methodological quality of such studies either from the reader's perspective or for the purpose of meta-analysis. The aim of the present study was to develop and validate such an instrument. METHODS: After an initial conceptualization phase of a methodological index for non-randomized studies (MINORS), a list of 12 potential items was sent to 100 experts from different surgical specialties for evaluation and was also assessed by 10 clinical methodologists. Subsequent testing involved the assessment of inter-reviewer agreement, test-retest reliability at 2 months, internal consistency reliability and external validity. RESULTS: The final version of MINORS contained 12 items, the first eight being specifically for non-comparative studies. Reliability was established on the basis of good inter-reviewer agreement, high test-retest reliability by the kappa-coefficient and good internal consistency by a high Cronbach's alpha-coefficient. External validity was established in terms of the ability of MINORS to identify excellent trials. CONCLUSIONS: MINORS is a valid instrument designed to assess the methodological quality of non-randomized surgical studies, whether comparative or non-comparative. The next step will be to determine its external validity when used in a large number of studies and to compare it with other existing instruments.

Clinical Trials as Topic↗
PubMed2003

Total vascular exclusion of the liver enhances the efficacy of retroviral-mediated associated thymidine kinase and interleukin-2 genes transfer against multiple hepatic tumors in rats.

BACKGROUND: Recent advances in gene transfer technology render gene therapy an attractive treatment of disseminated liver metastases for which other treatments remain disappointing. In this setting, total vascular exclusion of the liver could improve gene transfer to cancer cells and prevent extrahepatic vector spreading during portal infusion of therapeutic genes. We evaluate the efficiency of combined herpes simplex virus type-1 thymidine kinase (HSV1-TK) and interleukin-2 retrovirus-mediated gene transfer through the portal vein, under total vascular exclusion of the liver, in a model of macroscopic multiple liver metastases in rats. METHODS: Multifocal liver metastases were established in BDIX rats with intraportal injection of DHDK12 colon cancer cells. On randomization, rats received either vector-producing cells or saline solution under total vascular exclusion of the liver. Vector-producing cells released retroviral vectors encoding Lac-Z in marking studies or HSV1-TK or interleukin-2 in therapeutic studies. Rats were either killed for pathologic studies, or followed for survival. RESULTS: Total vascular exclusion of the liver markedly improved gene transfer efficacy in marking studies. In therapeutic studies we observed a significant reduction in tumor volume of treated rats compared with untreated controls (2170 +/- 310 mm(3)). Although singular HSV1-TK or interleukin-2 gene transfer showed significant efficacy, the greatest tumor volume regression was observed in rats treated with combined HSV1-TK + interleukin-2 gene therapy (145 +/- 60 mm(3); P =.0001 vs control). This translated into an increased median survival rate compared with either control rats (P =.006) or rats treated with single gene therapy. CONCLUSION: In a rat model, a significant antitumoral effect against macroscopic multifocal liver metastases can be observed after retrovirus-mediated HSV1-TK and interleukin-2 gene transfer through the portal vein under total vascular exclusion of the liver, followed by ganciclovir administration. We believe that this well-tolerated and efficient therapeutic approach deserves clinical evaluation in patients with disseminated colorectal liver metastases.

Animals↗
PubMed2002

Importance, mechanisms and limitations of the distant bystander effect in cancer gene therapy of experimental liver tumors.

GCV-ablation of transplanted TK-positive liver tumors or the application of syngenic and allogenic HSV-TK/GCV oncolysates significantly reduced the size of synchronously growing untreated sister tumors in the liver. These TK-negative liver tumors constantly showed an increased infiltration by mononuclears (x4). The relative abundance of CD 4/8, NK and monocyte subtypes remained constant. The distant bystander effect was associated with a strong induction of GMCSF and IL-12 expression in the untreated TK-negative liver tumors. Analysis of the vbeta T-cell receptor profiles from TK-negative tumors did not point to clonal lymphocyte expansions. These results support the view of the 'distant bystander effect' as a predominantly local phenomenon, which is mediated by resident immune effectors rather than by MHC I restricted CD 3 positive lymphocytes.

Adenoviridae↗
PubMed2002

Expression of endomembrane calcium pumps in colon and gastric cancer cells. Induction of SERCA3 expression during differentiation.

Calcium mobilization from the endoplasmic reticulum (ER) into the cytosol is a key component of several signaling networks controlling tumor cell growth, differentiation, or apoptosis. Sarco/endoplasmic reticulum calcium transport ATPases (SERCA-type calcium pumps), enzymes that accumulate calcium in the ER, play an important role in these phenomena. We report that SERCA3 expression is significantly reduced or lost in colon carcinomas when compared with normal colonic epithelial cells, which express this enzyme at a high level. To study the involvement of SERCA enzymes in differentiation, in this work differentiation of colon and gastric cancer cell lines was initiated, and the change in the expression of SERCA isoenzymes as well as intracellular calcium levels were investigated. Treatment of the tumor cells with butyrate or other established differentiation inducing agents resulted in a marked and specific induction of the expression of SERCA3, whereas the expression of the ubiquitous SERCA2 enzymes did not change significantly or was reduced. A similar marked increase in SERCA3 expression was found during spontaneous differentiation of post-confluent Caco-2 cells, and this closely correlated with the induction of other known markers of differentiation. Analysis of the expression of the SERCA3 alternative splice isoforms revealed induction of all three known iso-SERCA3 variants (3a, 3b, and 3c). Butyrate treatment of the KATO-III gastric cancer cells led to higher resting cytosolic calcium concentrations and, in accordance with the lower calcium affinity of SERCA3, to diminished ER calcium content. These data taken together indicate a defect in SERCA3 expression in colon cancers as compared with normal colonic epithelium, show that the calcium homeostasis of the endoplasmic reticulum may be remodeled during cellular differentiation, and indicate that SERCA3 constitutes an interesting new differentiation marker that may prove useful for the analysis of the phenotype of gastrointestinal adenocarcinomas.

Adenocarcinoma↗
PubMed2002

Factors associated with clinically significant anastomotic leakage after large bowel resection: multivariate analysis of 707 patients.

The aim of this study was to determine by univariate and multivariate analyses the factors associated with clinically significant anastomotic leakage (AL) after large bowel resection. From 1990 to 1997 a series of 707 patients underwent colonic or rectal resection (without a stoma). Patients were divided into two groups: those with clinical anastomotic leakage (group 1) and those without it (group 2). AL occurred in 43 of 707 patients (6%). The overall mortality was 2.2% and was significantly higher in patients with AL than in those without: 5 of 43 (12%) versus 11 of 664 (1.6%), p < 0.001. Univariate analysis showed 15 variables associated with the risk of AL: previous abdominal or pelvic irradiation (p = 0.02), American Society of Anesthesiologists (ASA) score > 2 (p = 0.04), leukocytosis (p = 0.02), renal failure (p = 0.03), steroid treatment (p = 0.01), duration of operation (p = 0.001), intraoperative septic conditions (p = 0.006), total colectomy (p = 0.009), transverse colectomy (p = 0.02), difficulties encountered during anastomosis (p = 0.001), ileorectal anastomosis (p = 0.02), colocolic anastomosis (p = 0.01), abdominal drainage (p = 0.05), and blood transfusion intraoperatively (p = 0.006) and postoperatively (p = 0.001). Multivariate analysis showed that only preoperative leukocytosis (p = 0.04), intraoperative septic conditions (p = 0.001), difficulties encountered during anastomosis (p = 0.007), colocolic anastomosis (p = 0.004), and postoperative blood transfusion (p = 0.0007) were independent factors associated with AL. The risk of AL increased from a range of 12% to 30% if one risk factor was present, to 38% with two factors, to 50% with three factors. After colorectal resection and intraperitoneal anastomosis, a temporary protective stoma is proposed in selected patients with high risk factors for AL, as observed in our study.

Adolescent↗
PubMed2002

Can failure of percutaneous drainage of postoperative abdominal abscesses be predicted?

BACKGROUND: Percutaneous drainage (PD) of complex postoperative abscesses associated with a variety of factors such as multiple location or enteric fistula remains a matter of debate. Accordingly, this retrospective study was designed to determine the predictive factors for failure of PD of postoperative abscess, in order to better select the patients who may benefit from PD. METHODS: From 1992 to 2000, the data of 73 patients who underwent computed tomography (CT)-guided PD for postoperative intra-abdominal abscess, were reviewed. PD was considered as failure when clinical sepsis persisted or subsequent surgery was needed. The possible association between failure of PD and 27 patient-, abscess-, surgical-, and drainage-related variables were assessed using univariate and multivariate analysis. RESULTS: Successful PD was achieved in 59 of 73 (81%) patients. The overall mortality was 3% but no patient died after salvage surgery. Multivariate analysis showed that only an abscess diameter of less than 5 cm (P = 0.042) and absence of antibiotic therapy (P = 0.01) were significant predictive variables for failure of PD. CONCLUSIONS: CT-guided PD associated with antibiotic therapy could be attempted as the initial treatment of postoperative abdominal abscesses even in complex cases such as loculated abscess or abscess associated with enteric fistula.

Abdominal Abscess↗
PubMed2002

Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study.

BACKGROUND: The diagnostic and therapeutic value of EGD in patients with upper GI bleeding is often limited by the presence of residual blood or clots. When infused before EGD, erythromycin, a potent gastrokinetic drug, might improve the quality of EGD in patients with upper GI bleeding. The aim of this study was to assess the effect of erythromycin on the quality of the EGD in patients with acute upper GI bleeding. METHODS: Forty-one patients admitted to the intensive care unit because of acute upper GI bleeding were included in a randomized, endoscopist-blinded, controlled trial, comparing erythromycin (3 mg/kg intravenously over 30 minutes) to no treatment (control patients). EGD was performed 30 to 90 minutes after the end of the infusion. The primary study outcome was quality of EGD examination, as evaluated on a scale of 0 to 3, and the need to perform a second diagnostic EGD within the next 8 days. Secondary outcomes were efficiency of the endoscopic hemostatic therapy and intensity of esophagogastroduodenal contractions, as evaluated on a scale of 0-3. RESULTS: The characteristics of the patients and lesions found by EGD were similar in both groups. Quality of the EGD examination was significantly better in the erythromycin group (n = 19) compared with the control group (n = 22) (2.5 [0.8] vs. 1.5 [1.3]; p = 0.02). Three patients receiving erythromycin required a second EGD compared with 10 control patients (p = 0.089). Erythromycin did not interfere with the performance of EGD or the efficiency of hemostatic procedures. The intensity of gastroduodenal contractions was similar in both groups. No adverse event was observed. CONCLUSIONS: In patients with acute upper GI bleeding, infusion of erythromycin before endoscopy significantly improved the quality of EGD and tended to reduce the need for second-look endoscopy.

Endoscopy, Digestive System↗
PubMed2002

AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression.

BACKGROUND: Excess advanced glycation end-products (AGEs) are formed during renal failure, and AGE formation also may be connected with the high glucose concentration of peritoneal dialysis (PD) fluids. To determine the effect of human peritoneal mesothelial cell (HPMC) exposure to glycated proteins, we studied the HPMC receptor of AGE expression (RAGE), and analyzed the results of AGE-RAGE interaction on adhesion molecule expression and leukocyte binding. METHODS: RAGE was detected by FACS analysis, and RAGE mRNA by reverse transcription-polymerase chain reaction (RT-PCR). Vascular and intercellular cell adhesion molecule (VCAM-1 and ICAM-1) expression was measured by a known radiometric technique under basal conditions, after the addition of an AGE-specific compound, Nepsilon-carboxylmethyllysine (CML-albumin). Leukocyte adhesion on HPMC was analyzed by videomicroscopy after HPMC stimulation. RESULTS: RAGE protein was detected on HPMC, and RAGE mRNA was evidenced by RT-PCR. VCAM-1 expression was stimulated by CML-albumin (P < 0.01), while ICAM-1 was unchanged. By blocking the AGE-RAGE interaction, anti-RAGE antibodies or recombinant RAGE inhibited the increase in VCAM-1 expression. CML-albumin stimulation potentiated leukocyte adhesion to HPMC (P < 0.001). This effect was prevented by the incubation of leukocytes with recombinant VCAM-1 (P < 0.001). CONCLUSIONS: AGE binding to RAGE stimulated mesothelial cell activity, and resulted in the overexpression of VCAM-1, a structure for leukocyte adhesion. The AGE-RAGE interaction resulted in HPMC activation, which may promote local inflammation, and thus is implicated in the peritoneal injury found in long-term PD patients.

Adult↗
PubMed2002

Colonoscopy accurately predicts the anatomical severity of colonic Crohn's disease attacks: correlation with findings from colectomy specimens.

OBJECTIVE: For the assessment of colonic Crohn's disease (CCD) attacks, no clinicobiological and/or morphological (endoscopic, radiological) criteria of severity have been validated in relation to anatomical criteria of severity (ACS) as a gold standard obtained from colectomy specimen examination. Our objective was to assess the accuracy of colonoscopy in predicting the anatomical severity grading of CCD. METHODS: Colectomy specimens from 78 consecutive patients operated between 1982 and 1996 for CCD resistant to medical treatment were analyzed and classified into two groups according to the presence (ACS+) or absence (ACS-) of ACS. These were defined as either deep ulcerations eroding the muscle layer, or mucosal detachments or ulcerations limited to the submucosa but extending to more than one third of one defined colonic segment (right, transverse, left colon). Three endoscopic criteria of severity (ECS) were then defined: 1) deep ulcerations eroding the muscle layer (ECS1), 2) deep ulcerations not eroding the muscle layer but involving more than one third of the mucosal area (ECS2), and 3) mucosal detachment on the edge of ulcerations (ECS3). RESULTS: According to colectomy specimen examination, 68 and 10 patients belonged to ACS+ and ACS- groups, respectively. ECS1, ECS2, and/or ECS3 were found in 70 patients. Positive predictive values of ECS1, ECS2, and ECS3 for the presence of ACS were 90%, 98%, and 92%, respectively. Negative predictive values were 43%, 72%, and 23% respectively. However, at least one ECS (ECS1, ECS2, or ECS3) was found in 95% of patients with ACS. The extent of ulcerations at colonoscopy was correlated to the results of colectomy specimen examination (p < 0.001). Taking into account only patients with ACS, 88% of those with at least one ECS were diagnosed through left side colonoscopy. Usual clinical and biological severity criteria were not different in ACS + and ACS- groups. Two cases of toxic megacolon and toxic shocks were observed after the colonoscopy. CONCLUSIONS: In experienced hands, colonoscopy can be useful in severe CCD attacks. When at least one ECS is found, colonoscopy predicts the anatomical severity of the colitis with a high probability. Conversely, when none of the three ECSs is found, colonoscopy can reasonably exclude the diagnosis of severe anatomical CCD.

Adolescent↗